Egger-class function

Egger Class

An object containing the estimate produced using the MR-Egger method as well as various statistics.

The MR-Egger model uses a random-effects model; a fixed-effect model does not make sense as pleiotropy leads to heterogeneity between the causal estimates targeted by the genetic variants. The (multiplicative) random-effects model allows over-dispersion in the regression model. Under-dispersion is not permitted (in case of under-dispersion, the residual standard error is set to 1). class

Slots

• Model: Model always takes the value random, as only random-effects analyses are permitted.
• Exposure: The name of the exposure variable.
• Outcome: The name of the outcome variable.
• Correlation: The matrix of correlations between genetic variants.
• Robust: Whether robust regression was used in the regression model relating the genetic associations with the outcome and those with the exposure.
• Penalized: Whether weights in the regression model were penalized for variants with heterogeneous causal estimates.
• Estimate: The causal point estimate from the MR-Egger method.
• StdError.Est: The standard error associated with Estimate.
• Pvalue.Est: P-value associated with the causal estimate from the Wald method.
• CILower.Est: The lower bound of the confidence interval for Estimate based on StdError.Est.
• CIUpper.Est: The upper bound of the confidence interval for Estimate based on StdError.Est.
• Intercept: The intercept estimate from the MR-Egger method. Under the InSIDE assumption, the intercept represents the average pleiotropic effect (average direct effect on the outcome) of a genetic variant. If the intercept differs from zero, this is evidence that the genetic variants are not all valid instruments; specifically, there is directional pleiotropy.
• StdError.Int: The standard error associated with Intercept.
• Pvalue.Int: P-value associated with the intercept from the Wald method.
• CILower.Int: The lower bound of the confidence interval for Intercept based on StdError.Int.
• CIUpper.Int: The upper bound of the confidence interval for Estimate based on StdError.Int.
• Alpha: The significance level used in constructing the confidence interval (default is 0.05).
• SNPs: The number of SNPs that were used in the calculation.
• Causal.pval: P-value associated with the causal estimate.
• Pleio.pval: P-value associated with the intercept (p-value for the MR-Egger intercept test of directional pleiotropy).
• RSE: The estimated residual standard error from the regression model.
• Heter.Stat: Heterogeneity statistic (Cochran's Q statistic) and associated p-value: the null hypothesis is that the MR-Egger regression model describes the associations with the outcome with no excess heterogeneity.
• I.sq: A measure of heterogeneity between the genetic associations with the exposure (see Bowden IJE 2016: "Assessing the suitability of summary data for Mendelian randomization analyses using MR-Egger regression: The role of the I2 statistic."). Low values of I.sq relate both to large differences in precision between MR-Egger and IVW estimates, and to more weak instrument bias (in a two-sample setting, this is attenuation of MR-Egger estimate towards the null).